Simultaneous detection of expression and gene mutations of HER2/neu in Chinese patients with gastric cancer

23 Background: CDH1 germline mutations are found to be associated with the development of hereditary diffuse gastric cancer (HDGC) and the early-onset diffuse gastric cancer (EODGC). But the impact of CDH1 gene mutations and large deletions on HDGC and EODGC has not been fully determined in Asians. Although the incidence of gastric cancer is relatively high in China, the detection rate of CDH1 germline mutations in Chinese patients with EODGC is rare compared to that in European patients. Methods: We investigated the mutation status of the CDH1 gene in 57 Chinese EODGC patients younger than 40 years old who met the clinical criteria for HDGC. Polymerase chain reaction-direct sequencing was performed, and multiplex ligation-dependent probe amplification (MLPA) was used to evaluate the patients with negative sequencing results. Associations between mutation, clinicopathologic, and overall survival data were analyzed by SPSS 19. Results: The germline mutations of CDH1gene were identified in 51 (89.5%) of the 57 EODGC patients. The nonsense mutation in exon 13 (c.2200T>C, p.Ala692*) occurred in fourty-six EODGC patients. The missense mutations were detected in twenty patients (Eighteen in exon 5: c.778G>C, p.Glu218Asp; Two in exon 12: c.2012C>G, p.Leu630Val). No deletion or duplication in any patient. Most of the patients carrying the CDH1 mutation in exon 13 had lymph node metastasis when compared with patients lacking CDH1 mutation (87.2% vs 60.0%) ( P < 0.05 ). EODGC patients, lacking germline CDH1 alterations, showed a longer median overall survival (mOS) than patients carrying CDH1 mutation in exon 13 ( P < 0.05 ). Moreover, the presence of CDH1 mutation in exon 13 was associated with the incidence of neural invasion ( P < 0.05 ). Conclusions: This study reveals novel CDH1 mutations in Chinese EODGC patients which had been poorly investigated. The presence of CDH1 mutation in EODGC patients may result in lymph node metastasis and poor prognosis. More research is needed to determine additional genetic targets that trigger EODGC.

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A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric cancer patients

10.21203/rs.3.rs-15940/v1 ◽

2020 ◽

Author(s):

Yinjie Zhang ◽

Yang Yang ◽

Qing Wei ◽

Ting Xu ◽

Xiaotian Zhang ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

High Risk ◽

Gene Mutations ◽

Genetic Alterations ◽

Chinese Patients ◽

Germline Variants ◽

High Risk Factors ◽

Uncertain Significance ◽

Gastric Cancer Patients

Abstract Background: Approximately 10% of patients with gastric cancer (GC) have a genetic predisposition for the disease. To date, knowledge regarding germline mutations in predisposing genes in the Chinese GC population is scarce. The aim of this study was to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. Methods: Forty patients from among ten families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands with pathogenic/likely pathogenic germline variants, Sanger sequencing was used to validate the variants in the probands and their relatives. Results: Sequencing indicated that 25% (10/40) of the patients carried a combined total of ten pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). Five of these variants have not previously been reported. In addition, a total of 129 variants of uncertain significance were identified in 27 patients. Conclusions: This study found that 25% of Chinese GC patients with hereditary high-risk factors have deleterious germline alterations. This result may indicate a unique genetic background of GC among Chinese patients.

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A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric cancer patients

10.21203/rs.2.18927/v1 ◽

2019 ◽

Author(s):

Yinjie Zhang ◽

Yang Yang ◽

Qing Wei ◽

Ting Xu ◽

Xiaotian Zhang ◽

...

Keyword(s):

Risk Factors ◽

Gastric Cancer ◽

High Risk ◽

Gene Mutations ◽

Genetic Alterations ◽

Chinese Patients ◽

Germline Variants ◽

High Risk Factors ◽

Uncertain Significance ◽

Gastric Cancer Patients

Abstract BackgroundApproximately 10% of patients with gastric cancer (GC) have a genetic predisposition for the disease. To date, knowledge regarding germline mutations in predisposing genes in the Chinese GC population is scarce. The aim of this study was to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer. Forty patients from among ten families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands with pathogenic/likely pathogenic germline variants, Sanger sequencing was used to validate the variants in the probands and their relatives.ResultsSequencing indicated that 25% (10/40) of the patients carried a combined total of ten pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). Five of these variants have not previously been reported. In addition, a total of 129 variants of uncertain significance were identified in 27 patients.ConclusionsThis study found that 25% of Chinese GC patients with hereditary high-risk factors have deleterious germline alterations. This result may indicate a unique genetic background of GC among Chinese patients.

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Rare and novel GNAS gene mutations in Chinese patients with thyroid cancer

Precision Medical Sciences ◽

10.1002/prm2.12039 ◽

2021 ◽

Author(s):

Zhuo Wang ◽

Changwen Jing ◽

Haixia Cao ◽

Jianzhong Wu ◽

Rong Ma

Keyword(s):

Thyroid Cancer ◽

Gene Mutations ◽

Chinese Patients ◽

Gnas Gene

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Gene Mutations in Epidermal Growth Factor Receptor Signaling Network and Their Association With Survival in Chinese Patients With Metastatic Colorectal Cancers

The Anatomical Record ◽

10.1002/ar.21202 ◽

2010 ◽

Vol 293 (9) ◽

pp. 1506-1511 ◽

Cited By ~ 8

Author(s):

Wangjun Liao ◽

Yulin Liao ◽

Jeff X. Zhou ◽

Jianming Xie ◽

Jinzhang Chen ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Gene Mutations ◽

Signaling Network ◽

Chinese Patients ◽

Colorectal Cancers ◽

Epidermal Growth ◽

Growth Factor Receptor Signaling

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Prophylactic total gastrectomy in hereditary diffuse gastric cancer: identification of two novel CDH1 gene mutations—a clinical observational study

Familial Cancer ◽

10.1007/s10689-013-9698-8 ◽

2014 ◽

Vol 13 (2) ◽

pp. 231-242 ◽

Cited By ~ 14

Author(s):

Linda Bardram ◽

Thomas V. O. Hansen ◽

Anne-Marie Gerdes ◽

Susanne Timshel ◽

Lennart Friis-Hansen ◽

...

Keyword(s):

Gastric Cancer ◽

Observational Study ◽

Total Gastrectomy ◽

Gene Mutations ◽

Hereditary Diffuse Gastric Cancer ◽

Diffuse Gastric Cancer ◽

Cdh1 Gene ◽

Prophylactic Total Gastrectomy

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Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab014 ◽

2021 ◽

Author(s):

Lingyun Zhang ◽

Zhixiang Ren ◽

Zhengzheng Su ◽

Yang Liu ◽

Tian Yang ◽

...

Keyword(s):

Thyroid Cancer ◽

Copy Number ◽

Treatment Strategies ◽

Gene Mutations ◽

Anaplastic Thyroid Cancer ◽

Chinese Patients ◽

Driver Gene ◽

Phosphatidylinositol 3 Kinase ◽

Entire Cohort ◽

Whole Exome

Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

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